Table 1.

Clinical presentation, genotype, N-carbamylglutamate (NCG) treatment and outcome of 34 patients reported to have NAGS deficiency

Family	Patient	Onset of symptoms	Presentation	Genotype	Onset of NCG therapy	Initial NCG dose	Chronic NCG dose	Outcome	Reference
1*	1	FH, 3d	Asymptomatic		10 d	100 mg/kg/d	180 mg/kg/d at 13 m	Ataxia, spasticity psychomotor retardation, death at 9 y	Bachman et al5 Bachman et al1 Schubiger et al45
2	2	6 d	Poor feeding, tachypnea, somnolence		N/A			Death at 8 d	Bachman et al17
3*	3	13 m	Decreased level of conciousness following febrile illness		N/A			Death at 13 m	Elpeleg et al22
4‡	4	5 w	Seizures following a viral gastroenteritis		N/A			Normal development at 18 m	Pandya et al27
	5	FH, 26 d	Diarrhea		N/A			Mild psychomotor retardation and spasticity at 6 m
5	6	2m	Frequent episodes of vomiting and lethargy, hypotonia		N/A			Profound psychomotor retardation at 2 y	Burlina et al18
6	7	4 y 10 m	Vomiting, lethargy hepatomegaly		N/A			Normal development at 5 y 7 m	Vockley et al34
7	8	3–4 d	Poor feeding, seizures	S410P/S410P	25 d	220 mg/kg/d	80 mg/kg/d at 1 y	Normal development at 1 y	Guffon et al24 Schmidt et al25
	9	FH, 1 d	Asymptomatic		1 d	1 14 mg/kg × 1 dose		Normal development	Guffon et al23
8	10	1.5 y	Confusion, combative behavior		20 y	60 mg/kg/d	50 mg/kg/d at 22 y	Cerebral dysfunction, paraplegia, incontinence at 22 y	Hinnie et al25
9	11	3–4 d	Poor feeding, vomiting, cycling movements and fist clenching		after 10 w	100 mg/kg/d	100 mg/kg/d at 20 m	Normal development at 20 m	Morris et al26
10	12	13 m	Vomiting, somnolence, hypotonia	A279P/A279P	13 y	100 mg/kg/d	100 mg/kg/d	IQ = 78 at 13 y	Plecko et al28 Haberle et al42
11	13	2.7 y	Paroxysmal crying, lethargy, meat and dairy aversion, "Reye syndrome" after valproate administration		4 y	100 mg/kg/d	100 mg/kg/d	Mental development <2 SD below age-matched controls at 4 y	Forget et al50
12	14	4d	Seizures, coma	c.1036insC/ c.1036insC	36 m	150 mg/kg/d	Not indicated	Psychomotor retardation at 4 y	Elpeleg et al22
	15	FH, 1 d	Asymptomatic		3 m	150 mg/kg/d	Not indicated	Psychomotor retardation at 2 y
13	16	<2 d	Tachypnea, jitteriness	W324X/W324X	N/A			Death at 4 d	Caldovic and Tuchman20
14	17	2 d	Lethargy, anorexia, vomiting, respiratory distress, coma, seizures	c.1025delC	N/A			Not indicated	Caldovic and Tuchman20
	15	2 d	Lethargy, anorexia, vomiting, respiratory distress, coma, seizures					Not indicated
15	19	3 d	Not indicated	c.1306insT/ IVS3-2A>T	N/A			Death at 3 d	Haberle et al42
16	20	3d	Not indicated	L430P/L430P	N/A			Not indicated	Haberle et al42 Schmidt et al25
17	21	6 d	Not indicated	E433S/E433S				Not indicated	Haberle et al42
18	22	3 d	Not indicated	W484R/W484R	N/A			Death at 6 m	Haberle et al42 Heckman et al32
19	23	4 d	Not indicated					Death at 22 d	Haberle et al42
	24	FH, 2 d	Asymptomatic	W324X/W324X	3 m	250 mg/kg/d	10–200 mg/kg/d	Normal at 13 y	Gessler et al4
20	25	9 y	Attention deficit, learning disabilities, episodes of anxiety and irritability		I2y	100 mg/kg/d	15 mg/kg/d	Not indicated	Belanger-Quintana étal13
21	26	4 w	Vomiting, irritability, lethargy	R509Q/IVS4-IG >C	N/A	NCG study 2.2 g/m2/d	Not indicated	Not indicated	Caldovic et al16 Caldovic et al"
	27	9 y	Lethargy, anorexia, vomiting					Not indicated
22	28	33 y	After surgery: hypertensive, combative, confused, seizures	V173E/T4311	N/A			Death at 33 y	Caldovic et al16
23	29	2.5 m	Vomiting, weight loss, hypotonia	C200R/C200R	4 m	180 mg/kg × 1 dose	Not indicated	Normal development, age not indicated	Schmidt et al25 Guffon et al23
24	30	2 d	Irritablity, poor feeding. By 4 d, drowsiness, tremor, hypotonia	A518T/A518T	4 d	200 mg/kg × 1 dose	Not indicated	Normal development, age not indicated	Schmidt et al25 Guffon et al23
25	21	27 y	Seizures, coma during pregnancy	L3I2P/T4311	N/A			Not indicated	Grody et al15 Caldovic et al14
26	32	3d	Seizures, coma	R414P/R414P	4 d	200 mg/kg/d	50 mg/kg/d at 3 y	Normal development at 3 y	Nordenstrom et al52
27	33	40 y	Migraine headaches, intermittent staring spells, nausea, recurrent vomiting, lethargy, ataxia, coma	V3501/L442V	N/A	NCG study 2.2 g/m2/d	Not indicated	Normal intellect at 57 y	Tuchman et al2
28	34	3d	Vomiting, feeding intolerance, episodic confusion	c.278delC/MI67V	6 m	350 mg/kg/d	23–140 mg/kg/d	Normal development at 20 y	Corne et al53

Notes: Familial hyperammonemia patients were identified prospectively based on a family history of hyperammonemia or N-acetylglutamate synthase deficiency (NAGS);

^*Older siblings died of hyperammonemia of unknown origin;

^‡Older brother died of seizures, liver failure.